2013
DOI: 10.2337/db13-0639
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Human Insulin Resistance Is Associated With Increased Plasma Levels of 12α-Hydroxylated Bile Acids

Abstract: Bile acids (BAs) exert pleiotropic metabolic effects, and physicochemical properties of different BAs affect their function. In rodents, insulin regulates BA composition, in part by regulating the BA 12α-hydroxylase CYP8B1. However, it is unclear whether a similar effect occurs in humans. To address this question, we examined the relationship between clamp-measured insulin sensitivity and plasma BA composition in a cohort of 200 healthy subjects and 35 type 2 diabetic (T2D) patients. In healthy subjects, insul… Show more

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Cited by 389 publications
(358 citation statements)
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“…Insulin regulates BA composition, in part by regulating the BA 12-α hydroxylase (CYP8B1), and it has been shown that a high ratio of 12α-hydroxylated / non-12α-hydroxylated BAs is associated with more insulin resistance [14]. A study of patients with type 2 diabetes observed, contrary to their hypothesis, an increase in this ratio after RYGB [28].…”
Section: Discussionmentioning
confidence: 42%
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“…Insulin regulates BA composition, in part by regulating the BA 12-α hydroxylase (CYP8B1), and it has been shown that a high ratio of 12α-hydroxylated / non-12α-hydroxylated BAs is associated with more insulin resistance [14]. A study of patients with type 2 diabetes observed, contrary to their hypothesis, an increase in this ratio after RYGB [28].…”
Section: Discussionmentioning
confidence: 42%
“…Furthermore, they regulate the balance of different species of the microbiome, and the microbiome interacts reciprocally with the metabolism and composition of BAs [8,9]. BAs have been suggested as important mediators of weight loss and metabolic changes after bariatric surgery [10][11][12][13], and different fractions of BAs have been linked to different features of glucose metabolism [14,15].…”
Section: Introductionmentioning
confidence: 99%
“…They showed that the intestinal FXR agonist fexaramine induces FGF 15, leading to alterations in bile acid composition, reduced diet-induced weight gain, and hepatic glucose production, while enhancing thermogenesis and browning of white adipose tissue. The absence of FXR has been shown to decrease the benefit of bariatric surgery on weight loss and glucose tolerance [12] . This is in keeping with the results of bile diversion to the distal small intestine, which also results in improved weight loss, glucose tolerance, and hepatic steatosis through a 10-fold increase in bile acids.…”
Section: The Forkhead Box Proteins (Foxo)mentioning
confidence: 99%
“…Haeusler and Astiarraga [12] have shown in 200 non-diabetic and 35 patients with type 2 diabetes that 12 α-hydroxylated/ non-12 α-hydroxylated bile acid ratio was associated with the key features of insulin resistance, including higher insulin, proinsulin, glucose, glucagon, and triglycerides with lower HDL cholesterol. In type 2 diabetes, bile acids were nearly two-fold elevated and more hydrophobic than healthy subjects.…”
Section: Bile Acid-activated Receptorsmentioning
confidence: 99%
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